Subjects with idiopathic uric acid nephrolithiasis had lower urine pH (5.5 versus 5.9; P,0.001) and
higher net acid excretion (60 versus 43 mEq/24 h; P,0.001), with the excess H+ carried by nonammonium
buffers. In all subjects, there was a positive relationship of net acid excretion with higher body mass index
in spite of strictly controlled equivalent dietary acid intake. This relationship was most evident among
control subjects (r=0.36; P=0.03). It was attenuated in patients with idiopathic uric acid nephrolithiasis
whose net acid excretion remained fixedly high and ammonium excretion remained low relative to net
acid excretion, resulting in low urine pH over a wide body mass index range. Urinary metabolomics was
performed to attempt to identify excess organic acids presented to the kidney in idiopathic uric acid
nephrolithiasis. Among the tricarboxylic acid cycle intermediates and amino acid and lipid metabolites
analyzed, 26 organic anions with acid dissociation constants values in the range of urine pH showed
greater protonation. However, protons carried by the identified organic acids did not entirely account for
the higher titratable acidity seen in idiopathic uric acid nephrolithiasis.
Conclusions:Higher acid load to the kidney, resulting in higher urinary net acid excretion, is an important factor in<br
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